scholarly journals Residual β-Cell Function in Type 1 Diabetes Followed for 2 Years after 3C Study

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Kun Lin ◽  
Xiaoping Yang ◽  
Yixi Wu ◽  
Shuru Chen ◽  
Qiong Zeng
Keyword(s):  
Cell Function ◽  
Cox Regression ◽  
Diabetic Patients ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
C Peptide ◽  
Cox Regression Analysis ◽  
Β Cell Function ◽  
Age Of Diagnosis

Objective. To investigate the natural history and related factors of the pancreatic β-cell function in Chinese type 1 diabetic patients from 3C study Shantou center. Method. Stimulated C-peptide levels from follow-up data of 201 individuals in 3C study Shantou subgroup starting in 2012 were used. Residual β-cell function was defined as stimulated C − peptide   level ≥ 0.2   pmol / mL , on the basis of cut-points derived from the Diabetes Control and Complications Trial (DCCT). Results. 36.8% of patients had residual β-cell function, and the percentage was 68.2% in newly diagnosed diabetic patients. COX regression analysis indicated that the age of diagnosis, HbA1C level, and duration were independent factors of residual β-cell function in individuals with ≤5 years duration, but in those with duration ≥5 years, only the age of diagnosis was a predictor. The pancreatic β-cell function mainly declined in the first 5 years of the duration, and the rate of decline was correlated negatively with the duration and age of diagnosis. Receiver operating characteristic (ROC) analysis indicated that the cut-off point of stimulated C-peptide was 0.615 pmol/mL in patients with <5 years duration to have 7% HbA1c. Conclusion. Age at diagnosis was the strongest predictor for residual C-peptide. There was a more rapid decline of stimulated C-peptide in duration ≤5 years and younger patients. Therefore, intervention therapies of β-cells should start from the early stage, and the recommended target goal of stimulated C-peptide is 0.615 pmol/mL or above.

scholarly journals Systemic TNFα correlates with residual β-cell function in children and adolescents newly diagnosed with type 1 diabetes

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Anne Julie Overgaard ◽  
Jens Otto Broby Madsen ◽  
Flemming Pociot ◽  
Jesper Johannesen ◽  
Joachim Størling
Keyword(s):  
Type 1 Diabetes ◽  
Cell Function ◽  
Disease Onset ◽  
Newly Diagnosed ◽  
Β Cell ◽  
Entire Study ◽  
C Peptide ◽  
Disease Remission ◽  
Β Cell Function

Abstract Background Type 1 diabetes (T1D) is caused by immune-mediated destruction of the β-cells. After initiation of insulin therapy many patients experience a period of improved residual β-cell function leading to partial disease remission. Cytokines are important immune-modulatory molecules and contribute to β-cell damage in T1D. The patterns of systemic circulating cytokines during T1D remission are not clear but may constitute biomarkers of disease status and progression. In this study, we investigated if the plasma levels of various pro- and anti-inflammatory cytokines around time of diagnosis were predictors of remission and residual β-cell function in children with T1D followed for one year after disease onset. Methods In a cohort of 63 newly diagnosed children (33% females) with T1D with a mean age of 11.3 years (3.3–17.7), ten cytokines were measured of which eight were detectable in plasma samples by Mesoscale Discovery multiplex technology at study start and after 6 and 12 months. Linear regression models were used to evaluate association of cytokines with stimulated C-peptide. Results Systemic levels of tumor necrosis factor (TNF)-α, interleukin (IL)-2 and IL-6 inversely correlated with stimulated C-peptide levels over the entire study (P < 0.05). The concentrations of TNFα and IL-10 at study start predicted stimulated C-peptide level at 6 months (P = 0.011 and P = 0.043, respectively, adjusted for sex, age, HbA1c and stage of puberty). Conclusions In recent-onset T1D, systemic cytokine levels, and in particular that of TNFα, correlate with residual β-cell function and may serve as prognostic biomarkers of disease remission and progression to optimize treatment strategies. Trial Registration The study was performed according to the criteria of the Helsinki II Declaration and was approved by the Danish Capital Region Ethics Committee on Biomedical Research Ethics (journal number H-3-2014-052). The parents of all participants gave written consent.

scholarly journals Frequent Monitoring of C-Peptide Levels in Newly Diagnosed Type 1 Subjects Using Dried Blood Spots Collected at Home

2018 ◽  
Vol 103 (9) ◽  
pp. 3350-3358 ◽  
Author(s):  
Ruben H Willemsen ◽  
Keith Burling ◽  
Peter Barker ◽  
Fran Ackland ◽  
Renuka P Dias ◽  
...  
Keyword(s):  
Cell Function ◽  
Dried Blood Spots ◽  
Diabetes Duration ◽  
Β Cell ◽  
C Peptide ◽  
Blood Spots ◽  
Β Cell Function ◽  
Over Time ◽  
At Home

Abstract Objective To evaluate an approach to measure β-cell function by frequent testing of C-peptide concentrations in dried blood spots (DBSs). Patients Thirty-two children, aged 7 to 17 years, with a recent diagnosis of type 1 diabetes. Design Mixed-meal tolerance test (MMTT) within 6 and again at 12 months after diagnosis, with paired venous and DBS C-peptide sampling at 0 and 90 minutes. Weekly DBS C-peptide before and after standardized breakfasts collected at home. Results DBS and plasma C-peptide levels (n = 115) correlated strongly (r = 0·91; P &lt; 0.001). The Bland-Altman plot indicated good agreement. The median number of home-collected DBS cards per participant was 24 over a median of 6.9 months. Repeated DBS C-peptide levels varied considerably within and between subjects. Adjustment for corresponding home glucose measurements reduced the variance, permitting accurate description of changes over time. The correlation of the C-peptide slope over time (assessed by repeated home DBS) vs area under the curve during the two MMTTs was r = 0.73 (P &lt; 0.001). Mixed models showed that a 1-month increase in diabetes duration was associated with 17-pmol/L decline in fasting DBS C-peptide, whereas increases of 1 mmol/L in glucose, 1 year older age at diagnosis, and 100 pmol/L higher baseline plasma C-peptide were associated with 18, 17, and 61 pmol/L higher fasting DBS C-peptide levels, respectively. In addition, glucose responsiveness decreased with longer diabetes duration. Conclusion Our approach permitted frequent assessment of C-peptide, making it feasible to monitor β-cell function at home. Evaluation of changes in the slope of C-peptide through this method may permit short-term evaluation of promising interventions.

Pancreatic β-cell function in cirrhotic patients with and without overt diabetes. C-peptide response to glucagon and to meal

Metabolism ◽  
1985 ◽  
Vol 34 (8) ◽  
pp. 695-701 ◽  
Author(s):  
G. Marchesini ◽  
A. Melli ◽  
G.A. Checchia ◽  
Loretta Mattioli ◽  
M. Capelli ◽  
...  
Keyword(s):  
Cell Function ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
C Peptide ◽  
Overt Diabetes ◽  
Β Cell Function ◽  
Cirrhotic Patients

scholarly journals Genetic Composition and Autoantibody Titers Model the Probability of Detecting C-Peptide Following Type 1 Diabetes Diagnosis

2021 ◽  
Author(s):  
MacKenzie D. Williams ◽  
Rhonda Bacher ◽  
Daniel J. Perry ◽  
C. Ramsey Grace ◽  
Kieran M. McGrail ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Disease Duration ◽  
Cell Function ◽  
Age At Onset ◽  
Diabetes Diagnosis ◽  
Β Cell ◽  
C Peptide ◽  
Peptide Detection ◽  
Β Cell Function

We and others previously demonstrated that a type 1 diabetes genetic risk score (GRS) improves the ability to predict disease progression and onset in at-risk subjects with islet autoantibodies. Here, we hypothesized that GRS and islet autoantibodies, combined with age at onset and disease duration, could serve as markers of residual β-cell function following type 1 diabetes diagnosis. Generalized estimating equations were used to investigate whether GRS along with insulinoma-associated protein-2 autoantibody (IA-2A), zinc transporter 8 autoantibody (ZnT8A) and GAD autoantibody (GADA) titers were predictive of C-peptide detection in a largely cross-sectional cohort of 401 subjects with type 1 diabetes (duration median = 4.5 years, range 0-60). Indeed, a combined model incorporating disease duration, age at onset, GRS, and titers of IA-2A, ZnT8A and GADA provided superior capacity to predict C-peptide detection (QIC=334.6) compared with disease duration, age at onset, and GRS as the sole parameters (QIC=359.2). These findings support the need for longitudinal validation of our combinatorial model. The ability to project the rate and extent of decline in residual C-peptide production for individuals with type 1 diabetes could critically inform enrollment and benchmarking for clinical trials seeking to preserve or restore endogenous β-cell function.

scholarly journals The Pathological Evolution of Glucose Response Curves During the Progression to Type 1 Diabetes in the TrialNet Pathway to Prevention Study

2020 ◽  
Author(s):  
Heba M. Ismail ◽  
Mario A. Cleves ◽  
Ping Xu ◽  
Ingrid M. Libman ◽  
Dorothy J. Becker ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Cell Function ◽  
Prevention Study ◽  
Β Cell ◽  
Response Curves ◽  
Glucose Response ◽  
Continuous Increase ◽  
C Peptide ◽  
Β Cell Function

<b>Objective: </b>Glucose response curves (GRCs) during oral glucose tolerance tests (OGTTs) are predictive of type 1 diabetes. We performed a longitudinal analysis in pancreatic autoantibody positive (Ab+) individuals to assess: 1) characteristic GRC changes during progression to type 1 diabetes, and 2) GRC changes in relation to β-cell function changes and to combined glucose and C-peptide response curve (GCRC) changes. <b>Research Design and Methods:</b> Among Ab+ individuals with serial OGTTs in the TrialNet Pathway to Prevention study, GRC changes from first to last OGTTs were compared between progressors (n=298) to type 1 diabetes and non-progressors (n=2216). GRC changes from last before diagnosis to diagnostic OGTTs were studied in progressors. <b>Results:</b> GRCs changed more frequently from Biphasic (2 peaks) to Monophasic (1 peak) GRCs between first and last OGTTs in progressors than in non-progressors [75.4% vs. 51.0%; p<0.001]. In contrast, progressors changed less frequently from Monophasic to Biphasic than non-progressors [12.6% vs. 30.6%; p <0.001]. Monotonic (continuous increase) GRCs were present in 47.7% of progressors at diagnosis. The early (30-0 min) C-peptide response decreased in progressors changing from Biphasic to Monophasic between first and last OGTTs (p<0.001) and from Monophasic to Monotonic between last and diagnostic OGTTs (p<0.001). Conversely, the early C-peptide response increased among non-progressors changing from Monophasic to Biphasic (p<0.001). Changes in GRCs were related to changes in GCRCs. <b>Conclusions:</b> Characteristic GRC changes, Biphasic to Monophasic to Monotonic, occur during the progression to type 1 diabetes. These GRC changes correspond to decreasing β-cell function.

scholarly journals Effects of incretin-based therapies on β-cell function in type 1 diabetes mellitus: a systematic review and meta-analysis

2021 ◽  
Vol 49 (12) ◽  
pp. 030006052110663
Author(s):  
Yucheng Wu ◽  
Yu Lu ◽  
Shufang Yang ◽  
Qingqing Zhang
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Plasma Glucose ◽  
Fasting Plasma Glucose ◽  
Cell Function ◽  
Meta Analysis ◽  
Β Cell ◽  
C Peptide ◽  
Β Cell Function

Aim To assess the effects of incretin-based therapies on β-cell function in patients with type 1 diabetes mellitus (T1DM). Methods We searched the PubMed, Cochrane Library, Embase, and Web of Knowledge databases for eligible randomized clinical trials published up to July 2021. The inclusion criteria were patients with T1DM or latent autoimmune diabetes in adults, patients treated with dipeptidyl peptidase-4 inhibitors or glucagon like peptide-1 receptor agonists, and outcomes included one of the following: fasting plasma glucose, fasting C-peptide, postprandial C-peptide, C-peptide area under the curve (AUC), homeostasis model assessment for β cell function, and insulin resistance. The effects were analyzed using a random effect model with STATA 11.0. Results Eight trials including 427 participants were included in the final analysis. A pooled analysis found no significant difference in fasting plasma glucose, fasting C-peptide, postprandial C-peptide, or C-peptide AUC between patients treated with incretin-based therapies and placebo. The two trials that reported changes in 2-hour postprandial C-peptide and two of the four trials that reported changes in C-peptide AUC reported increases after incretin-based therapies. Conclusion This meta-analysis showed that incretin-based therapies did not preserve β-cell function in patients with T1DM.

Pancreatic β-cell Function Is Associated with Augmented Counterregulation to In-Exercise Hypoglycemia in Type 1 Diabetes

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Olivia McCarthy ◽  
Jason Pitt ◽  
Max L. Eckstein ◽  
Othmar Moser ◽  
Stephen C. Bain ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Cell Function ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Β Cell Function
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